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Biology subjects

Bamman, M. M.

Publications and source records attributed to Bamman, M. M..

5 recordsLinked to original sources

Molecular Transducers of Physical Activity Consortium (MoTrPAC): Initial Insights into the Dynamic Human Responses to Exercise

The goal of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) is to examine the physiological and molecular basis for health benefits in response to acute and chronic exercise. Prior to COVID-19 suspension, healthy, sedentary participants (N=206, 18-74y) were randomized to endurance exercise (N=80), resistance exercise (N=81), or non-exercise control (N=45) interventions. The prescribed vigorous acute endurance and resistance exercise bouts induced physiological and metabolic perturbations relative to resting homeostasis. The supervised chronic (3d/wk, 12wk) endurance or resistance training programs robustly improved several physiological parameters (i.e., VO2peak, muscular strength). Temporal biospecimen (blood, muscle, and adipose) collections and processing coupled to the acute exercise bouts were highly successful. In most cases, over 90% success was achieved for blood, muscle, and adipose samples. Endurance and resistance exercise induced distinct acute and chronic physiological responses, which provide a framework to interrogate the molecular basis for health adaptations to these two popular exercise modalities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/705347v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@554ee9org.highwire.dtl.DTLVardef@afb28dorg.highwire.dtl.DTLVardef@f381cdorg.highwire.dtl.DTLVardef@cef19c_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

Effects of leg immobilization and recovery resistance training on skeletal muscle-molecular markers in previously resistance trained versus untrained adults

We sought to examine how resistance training (RT) status in young healthy individuals, either well-trained (T, n=10 (8 males)) or untrained (UT, n=11 (8 males)), affected muscle size and molecular markers with leg immobilization followed by recovery RT. All participants underwent two weeks of left leg immobilization via the use of crutches and a locking leg brace. After this two-week period, all participants underwent eight weeks (3 d/week) of knee extensor focused progressive RT. Vastus lateralis (VL) ultrasound-derived thickness and muscle cross-sectional area were measured at baseline (PRE), immediately after disuse (MID), and after RT (POST) with VL muscle biopsies collected at these time points. T and UT presented lower ultrasound derived VL size (cross-sectional area and thickness) values at MID versus PRE (p[&le;]0.001), and values increased in both groups from MID to POST (p<0.05); however, VL size increased from PRE to POST in UT only (p<0.001). Mean and type II myofiber cross-sectional area (fCSA) values demonstrated a main effect of time where PRE and POST were greater than MID (p<0.05) and main effect of training status where T was greater than UT (P[&le;]0.012). In both groups, satellite cell number was not affected by leg immobilization but increased in response to RT (p[&le;]0.014), with T being greater than UT across all time points (p=0.004). Additionally, ribosome content (total RNA) decreased (p=0.010) from PRE to MID while the endoplasmic reticulum stress proteins (BiP, Xbp1s, and CHOP) increased from MID to POST regardless of training status. Finally, the phosphorylation states of mechanistic target of rapamycin complex-1 signaling proteins were not significantly altered for either group throughout the intervention. In conclusion, immobilization-induced muscle atrophy and recovery RT hypertrophy outcomes are similar between UT and T participants, and the lack of molecular signature differences between groups supports these findings. However, these data are limited to younger adults undergoing non-complicated disuse. Thus, further investigation to determine the impact of training status on prolonged leg immobilization models mirroring current medical protocols (e.g., following orthopedic injury and surgery) is warranted.

physiology↗

Combined aerobic and resistance exercise training alters the spatial transcriptome of skeletal muscle in young adults

Chronic exercise training substantially improves skeletal muscle function and performance. The repeated demands and stressors of each exercise bout drive coordinated molecular adaptations within multiple cell types in muscle tissue, leading to enhanced neuromuscular recruitment and contractile function, stem cell activation, myofiber hypertrophy, mitochondrial biogenesis, and angiogenesis, among others. To comprehensively profile molecular changes induced by combined resistance and endurance exercise training, we employed spatial transcriptomics coupled with immunofluorescence and computational approaches to resolve effects on myofiber and mononuclear cell populations in human muscle. By computationally identifying fast and slow myofibers using immunofluorescence data of spatially sequenced tissue sections, we identified fiber type-specific, exercise-induced gene expression changes that correlated with muscle functional improvements. Additionally, spatial transcriptome profiling and integration of human muscle single cell RNAseq data identified an exercise-induced shift in interstitial cell populations coincident with angiogenesis. Overall, these data provide a unique spatial molecular profiling resource for exploring muscle adaptations to exercise, and provide a pipeline and rationale for future studies in human muscle.

physiology↗

Dynamic Transcriptomic Network Responses to Divergent Acute Exercise Challenges in Young Adults

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of adaptations in health, resilience, and performance. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to seek whole body health benefits. Mechanisms of action of these distinct doses are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD (n=21, 12M/9F, 22{+/-}3y) or HITT (n=19, 11M/8F, 22{+/-}2y). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR[&le;]0.05) immediately (h0, EVs only), h3, and h24 post-exercise within and between exercise doses. Additionally, all apparently responsive transcripts (FDR<0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and inter-regulatory relationships. LVs were compared across time and exercise dose. TRAD generally elicited a stronger, more consistent transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to divergent exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles in response to exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress. NEW AND NOTEWORTHYWe examined small and long transcriptomics in skeletal muscle and serum-derived extracellular vesicles before and after a single exposure to traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses to TRAD, whereas HITT elicited differential expression of microRNA enriched in brain regions. Follow-up analysis revealed relationships and temporal dynamics across transcript networks, highlighting potential avenues for research into mechanisms of exercise response and adaptation.

bioinformatics↗

miR-486 is an epigenetic modulator of Duchenne muscular dystrophy pathologies

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder resulting in muscle weakness and cardiomyopathy. MicroRNAs have been shown to play essential roles in muscle development, metabolism, and disease pathologies. We demonstrated that miR-486 expression is reduced in DMD muscles and its expression levels correlate with dystrophic disease severity. MicroRNA-486 knockout mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects that were exacerbated on the dystrophic mdx5cv background. We integrated RNA-sequencing and chimeric eCLIP-sequencing data to identify direct in vivo targets of miR-486 and associated dysregulated gene signatures in skeletal muscle. In comparison to our DMD mouse muscle transcriptomes, we identified several of these miR-486 muscle targets including known modulators of dystrophinopathy disease symptoms. Together, our studies identify miR-486 as a driver of muscle remodeling in DMD, a useful biomarker for dystrophic disease progression, and highlight chimeric eCLIP-sequencing as a useful tool to identify direct in vivo microRNA target transcripts. O_FIG O_LINKSMALLFIG WIDTH=122 HEIGHT=200 SRC="FIGDIR/small/448387v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@13eeaf5org.highwire.dtl.DTLVardef@1b3b2dborg.highwire.dtl.DTLVardef@a36782org.highwire.dtl.DTLVardef@1e0b95f_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗